Academic Journal
An OGT Missense Variant With Impaired Enzyme Activity in a Child With Severe Developmental Delay and Hepatoblastoma
| Τίτλος: | An OGT Missense Variant With Impaired Enzyme Activity in a Child With Severe Developmental Delay and Hepatoblastoma |
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| Συγγραφείς: | D'Alessio, Alfonso Manuel, Yuan, Huijie, Soria, Leandro Raul, Hansen, Sara Basse, Boffa, Iolanda, Arena, Paola, Attianese, Benedetta, O'Sullivan, Maureen, Cullinan, Noelle, Pang, Lewis, van Aalten, Daan Marinus Ferdinand, Brunetti-Pierri, Nicola, Lynch, Sally Ann |
| Πηγή: | D'Alessio, A M, Yuan, H, Soria, L R, Hansen, S B, Boffa, I, Arena, P, Attianese, B, O'Sullivan, M, Cullinan, N, Pang, L, van Aalten, D M F, Brunetti-Pierri, N & Lynch, S A 2026, 'An OGT Missense Variant With Impaired Enzyme Activity in a Child With Severe Developmental Delay and Hepatoblastoma', American Journal of Medical Genetics, Part A, vol. 200, no. 2, e64275, pp. 502-510. https://doi.org/10.1002/ajmg.a.64275 |
| Έτος έκδοσης: | 2026 |
| Συλλογή: | Discovery - University of Dundee Online Publications |
| Θεματικοί όροι: | congenital disorder of glycosylation, hepatoblastoma, intellectual disability, O-GlcNAc transferase, OGT variant, OGT-CDG, rare disease, /dk/atira/pure/subjectarea/asjc/1300/1311, name=Genetics, /dk/atira/pure/subjectarea/asjc/2700/2716, name=Genetics(clinical) |
| Περιγραφή: | O-GlcNAc transferase (OGT) and its antagonist O-GlcNAcase (OGA) regulate protein O-GlcNAcylation, a highly conserved post-translational modification involved in metabolic sensing. Pathogenic variants in the OGT gene cause an X-linked congenital disorder of glycosylation (OGT-CDG) presenting developmental delay, hypotonia, intellectual disability, and dysmorphic features. Here, we report on a child with developmental delay, hypotonia, and dysmorphic features who was found to carry a hemizygous novel OGT variant. This child also developed hepatoblastoma by the age of 17 months. OGT-CDG was diagnosed by exome sequencing that identified a de novo missense variant in the OGT gene. Functional validation by Western blot on patient-derived fibroblasts showed reduced O-GlcNAcylation and OGA expression, while significantly reduced enzyme activity in vitro confirmed the pathogenicity of the variant. To date, no patients with OGT-CDGs have been reported with hepatoblastoma or other malignancies. Although the occurrence of hepatoblastoma in the proband might be coincidental, the role of O-GlcNAcylation in cancer suggests that the deficiency of OGT activity might be associated with increased cancer risk. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | English |
| ISSN: | 1552-4825 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/41030119; info:eu-repo/semantics/altIdentifier/pissn/1552-4825 |
| DOI: | 10.1002/ajmg.a.64275 |
| Διαθεσιμότητα: | https://discovery.dundee.ac.uk/en/publications/07dd881c-5f65-46a5-85b3-d0444e18bd0c https://doi.org/10.1002/ajmg.a.64275 https://discovery.dundee.ac.uk/ws/files/158752421/American_J_of_Med_Genetics_Pt_A_-_2025_-_D_Alessio_-_An_OGT_Missense_Variant_With_Impaired_Enzyme_Activity_in_a_Child_With.pdf https://www.scopus.com/pages/publications/105017402558 |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Αριθμός Καταχώρησης: | edsbas.92C651C3 |
| Βάση Δεδομένων: | BASE |
| ISSN: | 15524825 |
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| DOI: | 10.1002/ajmg.a.64275 |